PROJECT SUMMARY This is an application for an Exploratory/Developmental Research Grant which brings together a team of engineers and clinician-scientists with expertise in ophthalmic imaging technology development and translation to advance the state of the art remote screening for diabetic retinopathy (DR). Diabetic retinopathy (DR) is a complication from diabetes mellitus (DM) that causes damage to the retinal vasculature. It is the leading cause of blindness in working age adults affecting approximately 100 million people worldwide. Despite this, DR remains highly treatable if detected early, with studies showing that early detection and treatment can reduce the risk of blindness by 95%. It is therefore recommended by the American Diabetes Association and the American Academy of Ophthalmology that all type 1 and type 2 diabetic patients have a comprehensive eye exam performed annually to screen for early signs of DR. The requirement for DR screening can be satisfied either through a clinical exam performed by an optometrist or ophthalmologist, or by acquiring a fundus photograph and having this photograph read by a qualified professional. The latter approach has spurned the creation of a market for telemedicine diabetic retinopathy screening companies who send technicians to visit patients in their homes, or in community clinics, to acquire images with handheld fundus cameras (HFCs). Unfortunately, gradability rates of these images can be quite poor, due to practical challenges in obtaining high quality images with an HFC. Many of the causes of poor gradability rates with HFCs can be significantly improved using confocal scanning laser ophthalmoscopy (cSLO). We hypothesize that using a handheld cSLO in screening applications would yield significantly superior readable rates as compared to HFCs. Under significant prior NIH and DOD support, our Duke team has become a worldwide leader in development of hand-held ophthalmic imaging technology for research applications, including a range of published designs for handheld cSLO, and optical coherence tomography devices, as well as adaptive optics enhanced versions of these devices. For this project, we propose to take advantage of this expertise to develop a relatively low-cost, high-performance hand-held SLO device optimized for remote screening of DR. The Scientific Premise of this proposal is that cSLO will be a superior imaging modality to HFCs for remote and telemedicine screening for DR. To investigate this hypothesis, we propose to construct a prototype widefield handheld cSLO device, verify its technical performance and validate its clinical suitability. We will then conduct a clinical study to compare the performance of the prototype cSLO device to existing commercial HFCs. The resulting improvement in gradability rates and effective sensitivity in DR screening could dramatically improve the standard of care in DR screening, facilitating earlier treatment of DR and potentially preventing millions of cases of blindness.